Project Summary /Abstract DNA makes RNA makes protein. The second step of that pathway ? the critical function of RNA in genetic information transfer ? is exquisitely regulated. mRNA activity, stability and location are controlled by factors that recognize specific RNA sequences. The PUF proteins are a widespread family of mRNA regulatory proteins that control key steps in early development and are required for establishing memory. They must find and recognize specific mRNAs, and then execute that mRNA's fate ? activation, repression, destruction, or movement. We elucidate the way in which these proteins form networks of control ? recognizing and controlling a substantial proportion of the mRNAs in human cells. They act through collaborations with protein partners ? interactions that are conserved from yeast to humans. PUF proteins and their partners have important roles in development, hoemostasis, cellular senescence, and human fertility. The networks of RNAs they control are vital in these processes.